The mammalian urinary bladder represents a unique model for the study of the interrelationships between smooth muscle function and autonomic innervation. Although the parasympathetic (cholinergic) system is considered to be the primary system involved in micturition control, sympathetic (adrenergic) innervation can modify and modulate bladder function. In addition to the neurohumoral control of bladder function, recent evidence indicates that bladder function may be modulated by a variety of hormones and bio-active peptides. We were the first to characterize the autonomic receptor distribution in the bladder. Utilizing current receptor binding and pharmacological methodology we will expand these studies to determine both the autonomic receptor subtypes present and which subtypes are responsible for the function response to specific receptor stimulation. Prior studies have demonstrated that acute administration of imipramine produces marked alterations in bladder function, using implanted osmotic pumps, we will determine the effect of chronic imipramine therapy on bladder innervation and function. Our studies on bladder overdistention, ischemia and obstruction indicate that the bladder responds with rapid compensatory alterations in bladder innervation, structure and function. We propose to systematically characterize these alterations for both acute and chronic pathological models. Results from these studies should provide significant new information on: normal bladder innervation and function, response to chronic pharmacological therapy, and response to specific pathologies.